Published in UAB Insight, Summer 2008
Long-term Health Implications; Donor Oocyte Program
Premature ovarian failure (POF) syndrome, which occurs in <1% of women, is defined by at least 4 months of amenorrhea, low levels of gonadal hormones, and hypergonadotropism in women aged <40 years. Early loss of ovarian function has significant psychosocial sequelae and long-term health considerations in addition to associated infertility. "Diagnosis and treatment require thorough evaluation and an empathetic approach," says UAB reproductive endocrinologist G. Wright Bates Jr, MD.
Women who experience spontaneous POF are at risk for numerous comorbidities. Ovarian failure may present as multiglandular dysfunction, including thyroid, adrenal, or pancreatic abnormalities. Parietal cell dysfunction, megaloblastic anemia, and fragile X syndrome also are associated with POF. Low estrogen levels at young ages place these women at risk for osteoporosis and cardiovascular disease. "Patients must weigh risks and benefits of hormone replacement therapy and take steps to avoid the consequences of early menopause. Early ovarian failure necessitates long-term surveillance to minimize health risks in later life," he says.
Etiopathogenic Mechanisms
"POF is a complex disease with multiple underlying etiopathogenic factors," Bates says. POF may be iatrogenic - from surgical ovary removal or damage due to radiation or chemotherapy - or spontaneous. In 90% of cases physicians cannot identify an etiology. Genetics may be a factor, such as with chromosome X defects in Turner syndrome and fragile X syndrome.
Recent studies have increasingly linked POF to autoimmune processes, and the disease is associated with a high incidence of autoimmune disorders, such as hypothyroidism, polyglandular autoimmune syndrome, and adrenal hormone insufficiencies such as Addison disease (Curr Opin Obstec Gynecol. 2007;19[4]:366-369).
"Ovarian depletion may result from a complex interaction of several different autoimmune mechanisms. This autoimmune component may account for the sporadic and intermittent return of ovarian function," Bates says. Between 5% and 10% of women with POF unexpectedly conceive.
This characteristic intermittent ovarian function in POF makes spontaneous pregnancy a possibility, but the unpredictability complicates family planning. No treatment exists to improve ovarian function. "A diagnosis of premature ovarian failure has a tremendous impact on a couples' desire to achieve a successful pregnancy," Bates says.
Options include adoption and assisted reproductive technologies with in vitro fertilization (IVF) using donor oocytes. UAB has reinstated its Donor Oocyte Program and has pregnancy rates that approach 60%. Couples may use eggs from an anonymous donor, a relative, or a friend. Extensive donor and recipient screening includes a detailed history and physical, a mental health screen, and blood testing for infections and genetic conditions such as cystic fibrosis, sickle cell, or Tay-Sachs disease. The program accepts women aged <32 years who do not smoke and have normal weight and healthy ovarian function (follicular stimulating hormone <8). Those with high-risk sexual behaviors, recent travel to third-world countries, tattoos, or body piercings may be excluded. "A donor egg IVF cycle is not without financial, physical, and emotional challenges for the couples who need this service, but it offers tremendous hope of achieving a pregnancy," Bates says.
FOR MORE INFORMATION:
Dr. Wright Bates
1.800.UAB.MIST
mist@uabmc.edu